The organization and control of expression of immunoglobulin genes are being investigated. Specifically, we are studying the evolution and organization of immunoglobulin lambda genes in mice. We have cloned all of the variable (V) and constant (C) genes of this locus, which we are now trying to link up by "chromosome walking." We are analyzing the specifics of lambda gene expression in SJL mice, which have a defect in lambda 1 synthesis. A nucleotide change in C lambda 1 is genetically linked with the defect. Additional DNA cloning, RNA and protein studies are aimed at determining the exact basis of the defect. Furthermore, we are studying the mechanisms of allelic exclusion and V-C gene rearrangement by gene transfection experiments. Finally, we are trying to determine the basis for the very localized somatic mutations in V genes which are expressed.